美国国立卫生研究院的Mario Roederer等研究人员合作揭示阿尔法病毒抗体保护的结构基础。相关论文于2023年6月8日发表于国际学术期刊《细胞》。
为了确定保护性抗体，研究人员用西部、东部和委内瑞拉马脑炎病毒样颗粒（VLP）的混合物对猕猴进行了免疫，这种方案可以防止所有三种病毒的气溶胶感染。单一和三重病毒特异性抗体被分离出来，研究人员确定了21个独特的结合组。Cryo-EM结构显示，广泛的VLP结合与序列和构象变化性成反比。一个三联特异性抗体SKT05与融合肽的近端结合，并通过使用不同的对称性元素来识别不同的VLP来中和所有三种包膜假型脑炎阿尔法病毒。研究人员在其他试验中的中和作用（如嵌合型Sindbis病毒）得到了不同的结果。SKT05与序列不同残基的骨架原子结合，尽管序列多变，仍能实现广泛的识别；因此，SKT05保护小鼠免受委内瑞拉马脑炎病毒、基孔肯雅病毒和罗斯河病毒的感染。因此，一个单一疫苗激发的抗体可以在体内保护小鼠免受广泛的阿尔法病毒的侵害。
据悉，阿尔法病毒是RNA病毒，代表着新兴的公共卫生威胁。
附：英文原文
Title: Vaccine elicitation and structural basis for antibody protection against alphaviruses
Author: Matthew S. Sutton, Sergei Pletnev, Victoria Callahan, Sungyoul Ko, Yaroslav Tsybovsky, Tatsiana Bylund, Ryan G. Casner, Gabriele Cerutti, Christina L. Gardner, Veronica Guirguis, Raffaello Verardi, Baoshan Zhang, David Ambrozak, Margaret Beddall, Hong Lei, Eun Sung Yang, Tracy Liu, Amy R. Henry, Reda Rawi, Arne Schn, Chaim A. Schramm, Chen-Hsiang Shen, Wei Shi, Tyler Stephens, Yongping Yang, Maria Burgos Florez, Julie E. Ledgerwood, Crystal W. Burke, Lawrence Shapiro, Julie M. Fox, Peter D. Kwong, Mario Roederer
Issue&Volume: 2023/06/08
Abstract: Alphaviruses are RNA viruses that represent emerging public health threats. To identifyprotective antibodies, we immunized macaques with a mixture of western, eastern, andVenezuelan equine encephalitis virus-like particles (VLPs), a regimen that protectsagainst aerosol challenge with all three viruses. Single- and triple-virus-specificantibodies were isolated, and we identified 21 unique binding groups. Cryo-EM structuresrevealed that broad VLP binding inversely correlated with sequence and conformationalvariability. One triple-specific antibody, SKT05, bound proximal to the fusion peptideand neutralized all three Env-pseudotyped encephalitic alphaviruses by using differentsymmetry elements for recognition across VLPs. Neutralization in other assays (e.g.,chimeric Sindbis virus) yielded variable results. SKT05 bound backbone atoms of sequence-diverseresidues, enabling broad recognition despite sequence variability; accordingly, SKT05protected mice against Venezuelan equine encephalitis virus, chikungunya virus, andRoss River virus challenges. Thus, a single vaccine-elicited antibody can protectin vivo against a broad range of alphaviruses.
DOI: 10.1016/j.cell.2023.05.019
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00538-X